Therapies, including hemofiltration, hemodiafiltration, and plasma pheresis, that require significant volumes of plasma water to be filtered and discarded require an equal or slightly smaller volume of fresh replacement fluid to be directly or indirectly infused into the patient's vascular compartment. In hemodialysis, for example, the infusion fluid is generally used to prime an extracorporeal circuit of a blood-cleansing machine, prior to connecting a patient to the machine, and to rinse the patient's blood at the end of the treatment. In the practice of hemodiafiltration, plasma water is removed by filtration from the blood as it traverses through the hemodialyzer cartridge. To compensate for this loss of plasma water, sterile fluid is added either upstream or downstream of the dialyzer cartridge. The sterile fluid used in these applications is generally a normal saline solution (e.g., a solution having a sodium chloride concentration of 0.9 percent by weight) which is supplied in flexible bags having predetermined volumes. In some cases, a Ringer's Lactate Solution may be used. In peritoneal dialysis, sterile peritoneal dialysis fluid packaged in flexible bags is typically infused into and subsequently emptied from the patient's peritoneal cavity.
The current state of the art employs one of two basic schemes for meeting the replacement infusion fluid requirements of such treatments. A commercially prepared solution intended for intravenous infusion is contained in a suitable reservoir, such as a flexible bag or a non-flexible vented bottle. The reservoir is connected to a fluid delivery assembly that includes a pump, such as a peristaltic pump and sterile tubing with appropriate connectors. The pump is used to create the required pressure differential between the fluid reservoir and a point of use (e.g., a blood and fluid mixing chamber) to assure the infusion fluid flow moves in a direction toward the point of use.
If an occlusive type pump is used, such as a peristaltic pump, an additional function of the pump is to assure that there is no retrograde flow of the patient's blood back into the sterile fluid reservoir. Due to pressure pulsations caused by the peristaltic pump, some retrograde flow of blood into the sterile tubing set occurs. Because of this, the sterile tubing set is disposed at the end of the treatment. Typically, in this arrangement, the sterile tubing set contains a special pump segment sized for the peristaltic pump. This results in a greater cost when compared to using a standard intravenous (IV) administration set.
A second strategy employed when larger volumes of fluid are required is to proportion water and salts to produce a solution that is similar in ionic content to plasma water as done by a dialysis machine to make dialysate. In this configuration, the dialysate solution or a portion of the solution must be treated (such as by filtration) to ensure it is of injectable quality prior to being used as a replacement or infusion fluid. Typically, a pump, such as a gear pump, peristaltic pump or piston pump is used to create the pressures required to move the required volume of fluid through the sterilizing filter(s) and to the point of use. Various articles describe many configurations of the substitution pump relative to the sterilizing filters in online hemodiafiltration systems. For example, in U.S. Pat. No. 4,702,829 ('829), to Polaschegg et al., which is incorporated herein by reference, the substitution pump is placed between two (redundant) sterilizing filters. The object of the '829 apparatus is to minimize the amount of negative pressure that would potentially occur if the pump were placed on the downstream side of the two sterilizing filters. In addition, this configuration allows the first filter to be operated in a cross-flow mode. The '829 patent does not address any means of preventing the final sterilizing filter (located between the venous drip chamber and the substitution pump) from being contaminated by blood products (red cells, proteins, etc.). For example, it is very common for blood to back-up in the drip chambers when pressures build up, such as when a blood line becomes kinked downstream of the drip chamber.
Though the infusion tubing segment between the final filter and the venous chamber may include a microfilter (e.g., 0.22 micron nominal pore size), it is understood by those skilled in the art that this microfilter does not prevent the final sterility filter from being contaminated by blood proteins when blood backs up into the infusion tubing set that is attached to the final sterility filter. Thus, it is implied that one would need to disinfect or sterilize the apparatus, including the final sterilization filter, before a new treatment is performed on the next patient.
In an article by Canaud, B. et al., “Hemodiafiltration Using Dialysate as Substitution Fluid”, Artificial Organs, Vol. 11(2), pp. 188-190, which is incorporated herein by reference, two different configurations are shown. In one configuration, the substitution pump is located before the two redundant sterilizing filters, while in the other configuration, the substitution pump is located between the two filters similar to that described in the '829 patent. The article fails to elaborate or teach the function of a stop valve which is shown in one of the figures. In addition, the article states that the machine and the infusate circuit is disinfected twice a day with perchloric acid and sterilized at the end of each day with 2.5 formalin. This implies that it is necessary to perform a disinfection process that includes the machine and the sterility filters between treatments in order to assure no cross contamination occurs between patients treated serially with the same system.
In U.S. Pat. No. 5,846,419 ('419) to Nederlof, which is incorporated herein by reference, two configurations are described. One configuration has the substitution pump between two sterilizing filters, while a second configuration has the substitution pump between the final sterilizing filter and the bloodline drip chamber. The '419 patent is directed to a method for preventing accumulation of germs and pyrogens on the upstream side of the sterility filters by enabling them to be operated in a cross-flow mode during treatment with these systems. The patent does not consider contamination of the downstream side of the final sterility filter such that can occur when blood backs up in the drip chamber shown in the figures of the patent.
In addition, there are several dialysis/diafiltration machines on the market that generate substitution fluid online using dialysate. In one system, the substitution pump is located between a second and third ultrafiltration or sterility filter. The third (final) sterility filter is part of the infusion set, thus the infusion set and final sterility filter is used only once to prevent any cross contamination. This type of system is embodied in a product commercially distributed under the trade name Gambro AK 200 Ultra™, from Gambro AB of Lund Sweden.
In a second system, the substitution pump is located after the final sterility filter. Because this system uses an occluding type (peristaltic) pump, it assures that no blood products will back up into the sterilizing filters. Therefore, disinfecting between treatments may not be required. The disadvantage of this system is that the system requires a special infusion tubing set that includes a dedicated pump segment for its operation. This infusion tubing set is accordingly more complex and costly than a standard IV administration set (that is typically used to prime the circuit with saline or for infusing sterile fluid into the blood circuit during dialysis treatment). Again, to prevent cross contamination, this special infusion tubing set is used once and is then discarded. An example of this type of system is a product system commercially available under the trade name Fresenius OnLine Plus™ System, available from Fresenius Medical Care of Bad Homburg, Germany.